[Federal Register: October 26, 2005 (Volume 70, Number 206)]
[Rules and Regulations]               
[Page 61736-61738]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26oc05-12]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2005P-0397]

 
Medical Devices; Immunology and Microbiology Devices; 
Classification of Cystic Fibrosis Transmembrane Conductance Regulator 
Gene Mutation Detection System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
cystic fibrosis transmembrane conductance regulator (CFTR) gene

[[Page 61737]]

mutation detection systems into class II (special controls). The 
special control that will apply to the device is the guidance document 
entitled ``Class II Special Controls Guidance Document: CFTR Gene 
Mutation Detection Systems.'' The agency is classifying the device into 
class II (special controls) in order to provide a reasonable assurance 
of safety and effectiveness of the device. Elsewhere in this issue of 
the Federal Register, FDA is announcing the availability of the 
guidance document that will serve as the special control for the 
device.

DATES: This final rule is effective November 25, 2005. The 
classification was effective May 9, 2005.

FOR FURTHER INFORMATION CONTACT: Zivana Tezak, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-0597.

SUPPLEMENTARY INFORMATION:

I. What is the Background of this Rulemaking?

    In accordance with section 513(f)(1) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 360c(f)(1)), devices that were not in 
commercial distribution before May 28, 1976, the date of enactment of 
the Medical Device Amendments of 1976 (the amendments), generally 
referred to as postamendments devices, are classified automatically by 
statute into class III without any FDA rulemaking process. These 
devices remain in class III and require premarket approval, unless and 
until the device is classified or reclassified into class I or class 
II, or FDA issues an order finding the device to be substantially 
equivalent, in accordance with section 513(i) of the act, to a 
predicate device that does not require premarket approval. The agency 
determines whether new devices are substantially equivalent to 
previously marketed devices by means of premarket notification 
procedures in section 510(k) of the act (21 U.S.C. 360(k)) and part 807 
(21 CFR part 807) of FDA's regulations.
    Section 513(f)(2) of the act provides that any person who submits a 
premarket notification under section 510(k) of the act for a device 
that has not previously been classified may, within 30 days after 
receiving an order classifying the device in class III under section 
513(f)(1) of the act, request that FDA classify the device under the 
criteria set forth in section 513(a)(1) of the act. FDA shall, within 
60 days of receiving such a request, classify the device by written 
order. This classification shall be the initial classification of the 
device. Within 30 days after the issuance of an order classifying the 
device, FDA must publish a notice in the Federal Register announcing 
such classification (section 513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on April 1, 2005, classifying the Tm Bioscience Corp., Tag-It\TM\ 
Cystic Fibrosis Kit into class III, because it was not substantially 
equivalent to a device that was introduced or delivered for 
introduction into interstate commerce for commercial distribution 
before May 28, 1976, or a device which was subsequently reclassified 
into class I or class II. On April 5, 2005, Tm Bioscience Corp., 
submitted a petition requesting classification of the Tag-It\TM\ Cystic 
Fibrosis Kit under section 513(f)(2) of the act. The manufacturer 
recommended that the device be classified into class II.
    In accordance with section 513(f)(2) of the act, FDA reviewed the 
petition in order to classify the device under the criteria for 
classification set forth in section 513(a)(1) of the act. Devices are 
to be classified into class II if general controls, by themselves, are 
insufficient to provide reasonable assurance of safety and 
effectiveness, but there is sufficient information to establish special 
controls to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use. After review of the 
information submitted in the petition, FDA determined that the Tm 
Bioscience Corp., Tag-It\TM\ Cystic Fibrosis Kit can be classified into 
class II with the establishment of special controls. FDA believes these 
special controls will provide reasonable assurance of safety and 
effectiveness of the device.
    The device is assigned the generic name ``cystic fibrosis 
transmembrane conductance regulator (CFTR) gene mutation detection 
system'' and it is identified as a device used to simultaneously detect 
and identify a panel of mutations and variants in the CFTR gene. It is 
intended as an aid in confirmatory diagnostic testing of individuals 
with suspected cystic fibrosis (CF), carrier identification, and 
newborn screening. This device is not intended for stand-alone 
diagnostic purposes, prenatal diagnostic, pre-implantation, or 
population screening. CFTR gene mutation detection systems may consist 
of different reagents and instruments, including polymerase chain 
reaction (PCR) primers, hybridization matrices, thermal cyclers, 
sequencers, signal detection instruments, and software packages.
    FDA has identified the risks to health associated specifically with 
this type of device as improper clinical recommendations and improper 
medical patient management due to failure of the test to perform as 
indicated or errors in interpretation of results. Specifically, in the 
context of carrier-screening in adults, a false-negative or false-
positive result or interpretation could lead to inaccurate estimates of 
a couple's risk of having a child with cystic fibrosis. In the context 
of assisting in the diagnosis of CF in newborns and children, a false-
negative could lead to a delay in the definitive diagnosis and 
treatment; a false-positive could lead to unnecessary or inappropriate 
treatment.
    FDA believes that the class II special controls guidance document 
aids in mitigating the potential risks to health by providing 
recommendations for validation of performance characteristics, as well 
as for labeling. The guidance document also provides information on how 
to meet premarket (510(k)) submission requirements for the device. FDA 
believes that the special controls guidance document, in addition to 
general controls, addresses the risks to health identified previously 
and provides reasonable assurance of the safety and effectiveness of 
the device. Therefore, on May 9, 2005, FDA issued an order to the 
petitioner classifying the device into class II. FDA is codifying this 
device by adding Sec.  866.5900.
    Following the effective date of this final rule, any firm 
submitting a 510(k) premarket notification for a CFTR gene mutation 
detection system will need to address the issues covered in the special 
controls guidance. However, the firm need only show that its device 
meets the recommendations of the guidance or in some other way provides 
equivalent assurance of safety and effectiveness.
    Section 510(m) of the act provides that FDA may exempt a class II 
device from the premarket notification requirements under section 
510(k) of the act, if FDA determines that premarket notification is not 
necessary to provide reasonable assurance of the safety and 
effectiveness of the device. For this type of device, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of the safety and effectiveness of the device and, 
therefore, the type of device is not exempt from premarket notification 
requirements. Persons who intend to market this type of device must 
submit to FDA a premarket notification, prior to marketing the device, 
which contains information about the CFTR gene

[[Page 61738]]

mutation detection system they intend to market.

II. What Is the Environmental Impact of This Rule?

    The agency has determined under 21 CFR 25.34(b) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

III. What Is the Economic Impact of This Rule?

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this final rule is not a significant regulatory action as defined by 
the Executive order and so it not subject to review under the Executive 
order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because classification of this device into class II 
will relieve manufacturers of the cost of complying with the premarket 
approval requirements of section 515 of the act (21 U.S.C. 360e), and 
may permit small potential competitors to enter the marketplace by 
lowering their costs, the agency certifies that the final rule will not 
have a significant economic impact on a substantial number of small 
entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $115 million using the most current (2003) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

IV. Does This Final Rule Have Federalism Implications?

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

V. How Does This Rule Comply with the Paperwork Reduction Act of 1995?

    FDA concludes that this rule contains no collections of 
information. Therefore, clearance by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 
U.S.C. 3501-3520) is not required.
    FDA also concludes that the special controls guidance document 
identified by this rule contains information collection provisions that 
are subject to review and clearance by OMB under the PRA. Elsewhere in 
this issue of the Federal Register, FDA is publishing a notice 
announcing the availability of the draft guidance entitled ``Class II 
Special Controls Guidance Document: CFTR Gene Mutation Detection 
Systems.''

VI. What References are on Display?

    The following reference has been placed on display in the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Petition from Tm Bioscience Corp., dated April 4, 2005.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, Medical devices.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
866 is amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

0
1. The authority citation for 21 CFR part 866 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
2. Add Sec.  866.5900 to subpart F to read as follows:


Sec.  866.5900  Cystic fibrosis transmembrane conductance regulator 
(CFTR) gene mutation detection system.

    (a) Identification. The CFTR gene mutation detection system is a 
device used to simultaneously detect and identify a panel of mutations 
and variants in the CFTR gene. It is intended as an aid in confirmatory 
diagnostic testing of individuals with suspected cystic fibrosis (CF), 
carrier identification, and newborn screening. This device is not 
intended for stand-alone diagnostic purposes, prenatal diagnostic, pre-
implantation, or population screening.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: CFTR Gene Mutation Detection System.'' See Sec.  
866.1(e) for the availability of this guidance document.

    Dated: October 17, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 05-21348 Filed 10-25-05; 8:45 am]

BILLING CODE 4160-01-S